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Focus on Newcastle - the search for a cure

Published on 01 July 2011
Source: Arthritis Today

Lab worker

As Newcastle Musculoskeletal Research Group celebrates its new European Centre of Excellence status, Arthritis Today provides a research update from Tyneside where Arthritis Research UK currently invests £6.5 million.

The burning question on the lips of everyone with arthritis is: where is the next “cure” going to come from?

The discovery of anti-TNF therapy by scientists at Arthritis Research UK’s Kennedy Institute more than a decade ago led to a worldwide revolution in the way that inflammatory arthritis was treated. Patients who once had few options beyond methotrexate were suddenly presented with a dazzling array of so-called biologic therapies that if not a cure, then enabled many of them to live near-normal lives.

But for the 30 per cent of people in whom anti-TNF and other biologic therapies don’t work, or can’t be tolerated, new approaches are needed.

And for sufferers of the most common type of arthritis, osteoarthritis, a side-effect-free form of pain relief or treatment to slow disease progression would be a welcome breakthrough.

A cure is generally agreed to be way off, if it happens at all.

Research… aims to induce remission

Research that aims to improve treatments and possibly edge nearer to a cure is going on in a number of universities and medical schools, largely funded by Arthritis Research UK. In particular, this is research that aims to induce remission in people with early inflammatory arthritis by using aggressive early biologic treatment, and identifying those people in whom this approach would be the most beneficial so that they can be targeted accordingly.

At Newcastle University, researchers at the Musculoskeletal Research Group are involved in work which they are confident will lead to if not a cure, then certainly better treatment for rheumatoid arthritis and osteoarthritis*, and are taking different approaches which could have significant outcomes for patients.

Professor John Isaacs“What we’re trying to do in Newcastle for rheumatoid arthritis patients is threefold – to improve the diagnosis and targeting of patients so they have a better outcome, to develop new therapies to switch off the disease (tolerogenic therapies), and experimenting with new cellular therapies,” explains professor of clinical rheumatology John Isaacs, whose specific field of experience and expertise is rheumatoid arthritis and therapeutic tolerance.

As regular readers of Arthritis Today will be aware, Professor Isaacs has been involved in setting up two exciting, experimental trials of potential new therapies for rheumatoid arthritis, both funded by Arthritis Research UK, and which attracted national media coverage when they were announced.

A real breakthrough

Neither has yet completed, but John Isaacs is hopeful that progress will have been made by the end of this year. One or both could produce a real breakthrough in treating rheumatoid arthritis, which is caused by the body’s immune system attacking joints, leading to inflammation.

In the first study, he and his team aim to develop a new cellular therapy that actually switches off a patient’s unwanted immune responses without suppressing protective immunity, which can leave people open to infections with other therapies.

Similar techniques have been used in cancer research (although in this situation the cells are designed to boost the anti-tumour immune response) but this will be the first time it has been adapted to rheumatoid arthritis and tested on patients. Twelve volunteers from the city’s Freeman Hospital will undergo the therapy as part of a pilot, which could then lead on to larger trials.

In a nutshell the team aims to chemically manipulate a patient’s own white blood cells and convert them into cells known as tolerogenic dendritic cells: cells which suppress immune system activity. They will then be injected back into the patient’s knee, and be followed up for three months. The hope is that the symptoms of rheumatoid arthritis will be effectively suppressed.

In the second study, co-funded by GlaxoSmithKline, the team has just started treating 40 rheumatoid arthritis patients with an anti-CD3 monoclonal antibody therapy called otelixizumab that could “switch off” the disease process, as part of a small phase 1 trial.

Could work as well as anti-TNF but will have a more sustained effect

The team hopes to establish that the drug – which has been trialled in type 1 diabetes – will be proven to be both safe and effective at specific doses. Patients will be given increasingly bigger doses as the trial progresses.

Professor Isaacs anticipates that otelixizumab could work as well as anti-TNF, but will have a more sustained effect from just a one-off course of treatment.

Professor Drew RowanDrew Rowan, professor of molecular rheumatology, a basic scientist who is working on related basic and translational research and in particular trying to understand inflammation and joint destruction in osteoarthritis, sounded a word of caution when talking about possible cures for that disease: “What we do in the laboratory today may take five to ten years before it starts to turn into potential treatment for patients,” he said.

“Understanding the disease process in arthritis is laborious, but we believe this knowledge will ultimately bear fruit.”


Plaudits for arthritis research in Newcastle

Scientists and clinicians involved in arthritis research at Newcastle University and the Freeman Hospital celebrated two prestigious accolades that confirm their status as leaders in their field.

The Musculoskeletal Research Group in the Faculty of Medical Sciences was awarded “Centre of Excellence” status by the European League Against Rheumatism (EULAR). The team was also recognised by Arthritis Research UK for its “outstanding contribution” to the charity in its 75th anniversary.

Dr Fraser Birell, a rheumatologist in Newcastle chats to a local branch memberThe Musculoskeletal Research Group comprises a large group of clinicians and scientists working together to improve the diagnosis, management and understanding of arthritic diseases. Their focus is a collaborative mix of basic science and clinical research projects aimed at addressing the problems of arthritis and age-related musculoskeletal diseases, alongside other specialist areas in paediatric rheumatology and education research.

EULAR, a European-wide scientific body whose chief aim is to stimulate research into arthritis and other musculoskeletal conditions, made the award to Newcastle on the basis of its impressive publications record in top academic journals. It is one of only six centres in the UK to have such status. Aberdeen and Glasgow Universities were also awarded Centre of Excellence status from EULAR this year.

Arthritis Research UK, which currently funds more than £6.5m into research in Newcastle, said its honouring of the group was an acknowledgement of its all-round outstanding contribution to the charity over a number of years which has seen them emerge as national leaders in a number of areas, for example:

• development of novel, experimental therapies for rheumatoid arthritis (Professor John Isaacs) 
• basic and translational research in osteoarthritis (Dean of Research Professor Tim Cawston and Professor Drew Rowan)
• leading a major genome screening project arcOGEN, aiming to find the genes that cause osteoarthritis (Professor John Loughlin)
• key aspects of research into arthritis affecting children and teenagers (Professor Helen Foster)
• educational research (Dr David Walker and Dr Lesley Kay)
• pioneering haematologic stem cell transplantation for scleroderma and other conditions (Professor Jaap van Laar).

The EULAR award, together with recognition from Arthritis Research UK, was presented at a special ceremony at the university in May and attended by local dignitaries, researchers, fundraisers and patients.

Professor Alan Silman, medical director of Arthritis Research UK, congratulated the group, telling his audience that they had made a phenomenal contribution to advancing the cause that the charity stood for, namely to relieve the suffering of people with arthritis. “We would not achieve our goals without people like you,” he added.

Professor Silman also warmly praised local fundraisers who attended the event from Yorkshire, Northumberland and Cumbria. “You are the engine room of this charity, and without your commitment to the cause none of this research would have been possible,” he said.

Professor John Isaacs said: “These achievements provide a wonderful endorsement of the hard work performed by numerous individuals over the past 15 years, as well as to the integration of the teams in the laboratory and in the clinic. It is a tough challenge to achieve international recognition in medical science but we deserve to be where we are.

“It is also fun to work at the ‘cutting edge’ and we aim to maintain our status by continuing to make important discoveries that impact on the management of musculoskeletal disease.”

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